Central nervous system abnormalities in Fanconi anemia

Fanconi anemia (FA) is associated with progressive bone marrow failure, cancer predisposition, and multiple congenital abnormalities. Brain atrophy and other abnormalities of the brain have also been reported, although the cause of these abnormalities and recommendations for clinical care are not yet defined. At the 2019 FA Scientific Symposium, Dr. Stella Davies from the University of Cincinnati and Dr. Tekin Aksu from Hacettepe University in Ankara, Turkey, presented on their recent work focused on central nervous system (CNS) abnormalities in people with FA. 

Dr. Davies discussed case reports of five FA patients with CNS abnormalities. Magnetic resonance imaging (MRI) of the brain showed that all five cases shared similar lesions and features of inflammation. The identified lesions were often ring-like in appearance, and all cases showed notable cerebellar involvement.  Four of the five patients had acute lesions and received dexamethasone (steroid) and had a significant response. Interestingly, immunohistochemical staining of brain biopsy tissue revealed expression of the JC virus. JC virus is one of three very similar polyomaviruses that affect humans (JC, BK and SV40 virus). 

Polyomaviruses are found in many individuals with FA, as well as in the non-FA population. The majority of people who harbor these viruses show evidence of exposure to the three viruses during childhood. In general, these viruses do not cause disease but can reactivate in immunosuppressed persons. JC virus reactivation in immunosuppressed persons causes brain inflammation that is called progressive multifocal leukoencephalopathy (PML). Dr. Davies’ research group hypothesizes that the brain lesions described in the five case studies result from inflammation caused by the JC virus. 

Dr. Aksu discussed a recent retrospective analysis of 314 FA patients treated at Hacettepe University from 1976 to 2019. Out of these 314 patients, 33 were evaluated with an MRI of the brain. The study found at least one abnormality in 18 patients of the study group. The abnormalities identified included density changes and reduced blood flow to the brain that led to brain cell damage. Dr. Aksu’s research group hypothesizes that these findings are related to impaired DNA repair mechanisms and/or congenital vascular malformations. 

These important studies highlight new clinical features in people with FA. More research is needed to understand how to best treat and prevent brain abnormalities from occurring. 

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